Increased Risk of Neutropaenia and Agranulocytosis with Sodium Valproate Used Adjunctively with Clozapine

Pantelis, Christos; Adesanya, Adesina

doi:10.1046/j.1440-1614.2001.0911f.x

Cited by 31 publications

(2 citation statements)

References 4 publications

(2 reference statements)

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“…Despite a low reported incidence of bone marrow suppression with valproate (0.4%), 8 a recent study found that co-administration of sodium valproate and clozapine is a significant risk factor for developing clozapine-associated neutropenia. 7 A number of case reports 10 – 12 have also described the phenomenon.…”

Section: Discussionmentioning

confidence: 98%

Clozapine-associated neutropenia following augmentation with sodium valproate

Jakobsen

Grønborg

Hansen

et al. 2021

SAGE Open Medical Case Reports

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Clozapine is gold standard for the management of treatment-resistant schizophrenia. It can offer life-changing symptom reduction where other antipsychotics have failed, and for these patients, treatment with clozapine should be maintained, if in any possible way. However, treatment with clozapine comes with a risk of developing potentially fatal adverse reactions, for example, severe neutropenia or agranulocytosis, in which case, treatment must be discontinued. Here, we present a case of clozapine-related neutropenia that commenced after the addition of sodium valproate. A subsequent re-challenge to clozapine resulted in severe neutropenia and led to the permanent cessation of clozapine treatment. The patient had been tolerating clozapine for more than a year before the addition of sodium valproate. The awareness of an interaction between clozapine and sodium valproate could help reduce the risk of clozapine-induced neutropenia and subsequent clozapine discontinuation.

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Section: Discussionmentioning

confidence: 98%

Clozapine-associated neutropenia following augmentation with sodium valproate

Jakobsen

Grønborg

Hansen

et al. 2021

SAGE Open Medical Case Reports

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“…[3][4][5][6][7][8][9][10][11][12][13][14] Several case reports of DVP-related neutropenia (absolute neutrophil count [ANC] < 1.50 10 3 /mcL) and leukopenia (white blood cell count [WBC] < 4.0 10 3 /mcL) were reviewed during our literature search, some caused by DVP monotherapy; others were thought to be related to concomitant use of DVP and another drug. [15][16][17][18][19][20][21][22][23][24][25] Quetiapine was the antipsychotic most commonly implicated in causing hematologic abnormalities when combined with DVP. We report a case of neutropenia and leukopenia that presented after a cross taper from quetiapine to DVP for the treatment of border-line personality disorder (BPD).…”

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confidence: 99%

Neutropenia and Leukopenia After Cross Taper From Quetiapine to Divalproex for the Treatment of Borderline Personality Disorder

Richmond¹

2022

Federal Practitioner

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Background: Valproic acid (VPA) and its derivative, divalproex (DVP) can cause various hematologic dyscrasias, the most common being thrombocytopenia. Neutropenia and leukopenia have been reported in isolated cases, most occurring in pediatric patients or patients with epilepsy. We report a case of leukopenia and neutropenia that presented after cross taper from quetiapine to DVP for the treatment of borderline personality disorder. Case presentation: A 34-year-old male patient with history of posttraumatic stress disorder, opioid use disorder, alcohol use disorder, stimulant use disorder, cannabis use, and borderline personality disorder underwent a cross taper from quetiapine to divalproex (DVP). DVP was titrated to 1000 mg per day, complete blood count (CBC) was obtained after completion of cross taper and revealed neutropenia and leukopenia with no documented history of blood dyscrasias. Nine days after discontinuation of DVP, neutrophil and white blood cell count returned to normal limits. With a score of 7 on the Naranjo Adverse Drug Reaction Probability Scale, an adverse reaction of probable DVP-induced neutropenia was documented and medication was not resumed. Conclusions: This case suggests that there may be a correlation between DVP and isolated neutropenia and leukopenia. Although a CBC is collected routinely to monitor for thrombocytopenia, health care practitioners also should consider other blood dyscrasias. Further studies are warranted to determine incidence of neutropenia and leukopenia with DVP therapy and evaluate whether the medication can be safely continued in cases of mildto-moderate neutropenia with close monitoring.

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